Alcohol effects on the percentage of beta waves in the electroencephalograms of twins

Electroencephalogram (EEG) recordings were made from 26 pairs of monozygotic (MZ) and 26 pairs of dizygotic (DZ) adult male twins, before and after alcohol ingestion. After a baseline EEG and a light breakfast, 1.2 ml/kg of ethanol was given orally over 15 min and the EEG repeated four times at hourly intervals. Alcohol caused a significant drop in the percentage of beta waves (14-30 cycles/sec) during the 1st hr. For the percentage of beta waves in 38 pairs of twins with complete data, MZ twin beta-wave intraclass correlations (RMZ) ranged between 0.85 and 0.91 before and after alcohol, but the DZ intraclass correlations (RDZ) started at 0.54 and fell to 0.05 at 2 hr after alcohol before recovering to baseline levels. These correlations resulted in heritability estimates [2(RMZ-RDZ)] of 0.68 at baseline and 1.73 at 2 hr. A heritability of 1.43 was found for the 1st hr drop in percentage of beta waves (RMZ = 0.78, RDZ = 0.06). These unrealistically high heritabilities, due to RDZ's approaching 0.0, suggest a failure of assumptions in the linear twin model that was used. Also, these findings are similar to, but more exaggerated than, findings in resting EEG's and visually evoked EEG potentials of twins and are compatible with the influence of gene interactions.     

Demonstration of extrachromosmal DNA fromBabesia equi merozoites

An extrachromosomal nucleic acid element was detected in high-molecular-weight DNA preparations formBabesia equi merozoites. This extrachromosomal element was shown to be DNA rather than RNA and had an apparent fragment size of about 9 kilobasepairs (kb). Hybridization experiments using purified 9-kb DNA as a probe revealed sequence homologies with extrachromosomal DNA from two otherBabesia species.     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Image-guided aspiration of solitary occult breast 'cysts'.

During the 30-month period from March 1, 1988, through August 31, 1990, image-guided aspirations of 183 solitary occult breast masses, which were considered possible cysts, were performed. Indications for aspiration included (1) mass on mammography, either invisible on ultrasonography or with features atypical of a cyst, in 111 patients; (2) enlarging solitary mass on mammography with ultrasonic features suggesting a cyst in 45 patients; and (3) mammographic mass with features typical of a cyst in 27 patients, with confirmation requested by the referring physician. Of the group, 151 (83%) lesions were fluid-filled and 32 (17%) were solid. All aspirates had normal cytologic features. Of the 32 aspirates found to be solid, 19 were subsequently removed after wire localization and 13 were unchanged on mammography for a minimum of 6 months after aspiration. This is a simple and safe procedure, confirming the innocuous nature of an occult solitary breast cyst, and obviates the need for surgical biopsy.     

Detection of the Arg702Trp, Gly908Arg and Leu1007fsinsC polymorphisms of the NOD2/CARD15 gene by real-time PCR with melting curve analysis.

Crohn's disease is a complex disorder, with multiple genetic traits. A frameshift mutation (Leu1007fsinsC) and two missense mutations (Gly908Arg and Arg702Trp) in the NOD2/CARD15 gene are strongly associated with susceptibility to Crohn's disease. The presence of one of these risk alleles confers a 2- to 4-fold increase in the risk of developing Crohn's disease, and the presence of two mutant alleles increases the risk over 20-fold. To facilitate the analysis of these polymorphisms, we developed three LightCycler assays to detect the missense mutations Arg702Trp and Gly908Arg and the frameshift mutation Leu100fsinsC in the NOD2/ CARD15 gene. All three assays can be run simultaneously on one LightCycler using identical cycling parameters. Analysis of 53 DNAs from Crohn's patients helped to identify carriers at allele frequencies similar to other Caucasian populations. The sequencing of such DNAs confirmed the accuracy of the assays. In conclusion, we present three rapid and robust assays to detect the Arg702Trp, the Gly908Arg and the Leu1007fsinsC ins mutations in the NOD2/CARD15 gene [corrected]     

Adeno-associated virus vector-mediated systemic delivery of IFN-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models.

PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression.